A New MRI Measure to Early Differentiate Progressive Supranuclear Palsy From De Novo Parkinson's Disease in Clinical Practice: An International Study

Abstract

Background: Enlargement of the third ventricle has been reported in atypical parkinsonism. We investigated whether the measurement of third ventricle width could distinguish Parkinson's disease (PD) from progressive supranuclear palsy (PSP).

Methods: We assessed a new MR T1-weighted measurement (third ventricle width/internal skull diameter) in a training cohort of 268 participants (98 PD, 73 PSP, 98 controls from our center) and in a testing cohort of 291 participants (82 de novo PD patients and 133 controls from the Parkinson's Progression Markers Initiative, 76 early-stage PSP from an international research group). PD diagnosis was confirmed after a 4-year follow-up. Diagnostic performance of the third ventricle/internal skull diameter was assessed using receiver operating characteristic curve with bootstrapping; the area under the curve of the training cohort was compared with the area under the curve of the testing cohort using the De Long test.

Results: In both cohorts, third ventricle/internal skull diameter values did not differ between PD and controls but were significantly lower in PD than in PSP patients (P < 0.0001). In PD, third ventricle/internal skull diameter values did not change significantly between baseline and follow-up evaluation. Receiver operating characteristic analysis accurately differentiated PD from PSP in the training cohort (area under the curve, 0.94; 95% CI, 91.1-97.6; cutoff, 5.72) and in the testing cohort (area under the curve, 0.91; 95% CI, 87.0-97.0; cutoff,: 5.88), validating the generalizability of the results.

Conclusion: Our study provides a new reliable and validated MRI measurement for the early differentiation of PD and PSP. The simplicity and generalizability of this biomarker make it suitable for routine clinical practice and for selection of patients in clinical trials worldwide. © 2020 International Parkinson and Movement Disorder Society.

Keywords: MRI biomarker; Parkinson's disease; clinical practice; progressive supranuclear palsy; third ventricle width.

FIG. 1.

Subcallosal axial T1-weighted volumetric MR images showing the measurement of the third ventricle width and the internal skull diameter (ID) in (A) a patient with progressive supranuclear palsy (PSP), (B) a patient with Parkinson’s disease (PD), and (C) a control subject. (D) Axial slices generated using the subcallosal line on 3-D T1-weighted sagittal images. Measurements were performed at the level of the third ventricle’s maximum dilatation as the largest left-to-right width between the lateral borders of the ventricle in its central portion. The maximum ID was also measured on the same axial slice. The third ventricle width was normalized dividing by the ID, and the ratio value was multiplied by 100. Images show marked dilatation of the third ventricle in the PSP patient compared with the PD patient and the control subject.

FIG. 2.

Probability of having PSP or PD for each 3^rdV/ID value in the training (red) and testing (blue) cohorts obtained using logistic regression models. The probability of having PSP increased with higher 3^rdV/ID values, whereas the probability of having PD decreased with larger 3^rdV/ID values. There were no differences between the logistic regression models obtained in the training and testing cohorts (P = 1).

FIG. 3.

Receiving operating characteristic (ROC) curves for the 3^rdV/ID in differentiating between PSP and PD patients, in the training cohort (red) and in the testing cohort (blue). The training cohort included 73 PSP patients and 98 PD patients; the testing cohort included 76 PSP patients and 82 PD patients.3^rdV/ID, third ventricle width/internal skull diameter; AUC, area under the curve.